【摘要】 探讨PPI1基因在裸鼠体内对人宫颈癌细胞生长的抑制作用。首先将稳定表达PPI1野生型和突变活化型基因的人宫颈癌细胞HeLa进行裸鼠体内致瘤,观察PPI1对肿瘤生长的影响;其次构建野生型HeLa细胞宫颈癌裸鼠模型,通过在体电脉冲技术,将PPI1野生型和突变活化型基因导入瘤体内进行基因治疗,观察裸鼠的存活情况;FACS分析移植瘤的细胞周期分布;免疫组化法检测移植瘤中的PPI1、cyclin B1、p53和p21的表达水平。在致瘤实验中,稳定表达PPI1突变活化型基因的HeLa细胞组的瘤结节生长缓慢,瘤结节明显小于对照组;在基因治疗实验中,PPI1突变活化型基因治疗组的裸鼠生存期明显延长,瘤组织中的肿瘤细胞呈现G2/M期停滞,cyclin B1和p21的表达水平明显增强,而突变型p53的表达明显减弱。PPI1活化型突变体对裸鼠HeLa移植瘤生长有明显的抑制作用。更多还原

【Abstract】 This article is to investigate the effects of PPI1 gene on the tumorigenesis of human cervix carcinoma cell line HeLa in nude mice. Firstly, wild type and activated mutant of PPI1 gene stable transfected HeLa cells were injected into nude mice. The effects of PPI1 gene on the tumorigenesis were observed. Secondly,wild type HeLa cells were injected into nude mice to establish the xenograft tumor model, then wild type and activated mutant of PPI1 gene were delivered into tumors by electroporation in vivo. The therapeutic effects of PPI1 gene were observed, and the cell cycle of the xenograft tumor cells was analyzed by FACS, the expression of PPI1, cyclin B1, p53 and p21 were detected by immunohistochemistry. In nude mice, the tumorigenesis of HeLa cell transfected with PPI1 activated mutant gene was inhibited markedly. After intratumoral gene transfer of PPI1 activated mutant gene, the survival of HeLa-bearing nude mice is prolonged significantly, and HeLa cells were arrested in G2/M, with up-regulation of cyclin B1 and p21, down-regulation of p53 mutant.Conclusion PPI1 activated mutant gene has significant inhibitory effect on human cervix carcinoma cell line HeLa solid tumors formed in nude mice.更多还原